chapter  9
42 Pages

Impact of Physicochemical Properties on Dendrimer Pharmacokinetics and Biodistribution

Given that dendrimers are macromolecular entities with a highly defined structure and low polydispersity, there has been increasing interest over the past 20 years in developing dendrimer-based drug delivery and imaging systems. The significant potential of dendrimers to modulate and improve the biological and pharmacokinetic properties of associated drugs and imaging moieties has inspired the synthesis of some very elegant and elaborate constructs with multiple in vivo functionalities. The translatability of these novel constructs into clinical application is ultimately, however, dependent largely upon their chemical and biological reproducibility, toxicological and pharmacokinetic properties. The pharmacokinetic and biodistribution behavior of dendrimers in particular is largely dictated by physicochemical properties, such as size, hydrophilicity, surface charge, functionality,

flexibility and core or scaffold structure. As a general guideline, very large, hydrophobic or anionic dendrimers avidly target organs of the mononuclear phagocyte system which contain high levels of macrophages, such as the liver, spleen, lungs and lymphoid tissue. Small hydrophilic, flexible or uncharged systems are more readily eliminated from the body via urinary excretion, whilst larger hydrophilic and uncharged systems tend to remain in the body for prolonged periods of time and facilitate uptake into solid tumors or areas of inflammation and increased angiogenesis. This chapter therefore gives an overview of our current understanding of the pharmacokinetic and biodistribution behavior of dendrimers, and how this can be dictated by physicochemical properties.